Abstract
Safrole is a carcinogen found in plants. The effect of safrole on cytosolic free Ca 2+ concentrations ([Ca 2+ ]i) and viability in SCM1 human gastric cancer cells was explored. The Ca 2+ -sensitive fluorescent dye fura-2 was applied to measure [Ca 2+ ]i. Safrole at concentrations of 150-450 μM induced a [Ca 2+ ]i rise in a concentration-dependent manner. The response was reduced by 60% by removing extracellular Ca 2+ . Safrole-evoked Ca 2+ entry was not altered by nifedipine, econazole, SKF96365, and protein kinase C activator or inhibitor. In Ca 2+ -free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished safrole-evoked [Ca 2+ ]i rises. Conversely, treatment with safrole abolished thapsigargin or BHQ-evoked [Ca 2+ ]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished safrole-induced [Ca 2+ ]i rises. At 250-550 μM, safrole decreased cell viability concentration-dependently, which was not reversed by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that safrole (350-550 μM) induced apoptosis concentration-dependently. These studies suggest that in SCM1 human gastric cancer cells, safrole induced [Ca 2+ ]i rises by inducing PLC-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via non-store-operated Ca 2+ entry pathways. Safrole-induced cell death may involve apoptosis.
Original language | English |
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Pages (from-to) | 302-311 |
Number of pages | 10 |
Journal | Chinese Journal of Physiology |
Volume | 58 |
Issue number | 5 |
DOIs | |
State | Published - 2015 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2015 by The Chinese Physiological Society and Airiti Press Inc.
Keywords
- Apoptosis
- Ca
- Endoplasmic reticulum
- Human gastric cancer cells
- Phospholipase C
- Safrole